145-568: In epidemiology , the basic reproduction number , or basic reproductive number (sometimes called basic reproduction ratio or basic reproductive rate ), denoted R 0 {\displaystyle R_{0}} (pronounced R nought or R zero ), of an infection is the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. The definition assumes that no other individuals are infected or immunized (naturally or through vaccination ). Some definitions, such as that of
290-456: A prion . The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is likely to be benign . The diagnosis is aided by the presenting symptoms in any individual with an infectious disease, yet it usually needs additional diagnostic techniques to confirm the suspicion. Some signs are specifically characteristic and indicative of
435-422: A runny nose . In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier . An infection is not synonymous with an infectious disease, as some infections do not cause illness in
580-437: A causal association does not exist in general. Conversely, it can be (and is in some circumstances) taken by US courts, in an individual case, to justify an inference that a causal association does exist, based upon a balance of probability . The subdiscipline of forensic epidemiology is directed at the investigation of specific causation of disease or injury in individuals or groups of individuals in instances in which causation
725-425: A colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and Viridans streptococci , prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with
870-514: A defined population . It is a cornerstone of public health , and shapes policy decisions and evidence-based practice by identifying risk factors for disease and targets for preventive healthcare . Epidemiologists help with study design, collection, and statistical analysis of data, amend interpretation and dissemination of results (including peer review and occasional systematic review ). Epidemiology has helped develop methodology used in clinical research , public health studies, and, to
1015-469: A disease and are called pathognomonic signs; but these are rare. Not all infections are symptomatic. In children the presence of cyanosis , rapid breathing, poor peripheral perfusion, or a petechial rash increases the risk of a serious infection by greater than 5 fold. Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C. Many diagnostic approaches depend on microbiological culture to isolate
1160-399: A disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers , are derived from the genomes of infectious agents, and with time those genomes will be known if they are not already. Thus, the technological ability to detect any infectious agent rapidly and specifically
1305-417: A fully mixed population with no structured relations between the individuals. For example, if there is some correlation between people's immunization (e.g., vaccination) status, then the formula 1 − 1 / R 0 {\displaystyle 1-1/R_{0}} may underestimate the herd immunity threshold. The basic reproduction number is affected by several factors, including
1450-498: A health system responds to current population health issues but also how a health system can be managed to better respond to future potential population health issues. Examples of organizations that use population-based health management that leverage the work and results of epidemiological practice include Canadian Strategy for Cancer Control, Health Canada Tobacco Control Programs, Rick Hansen Foundation, Canadian Tobacco Control Research Initiative. Each of these organizations uses
1595-423: A hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community. One manner of proving that a given disease is infectious, is to satisfy Koch's postulates (first proposed by Robert Koch ), which require that first, the infectious agent be identifiable only in patients who have the disease, and not in healthy controls, and second, that patients who contract
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#17327794809571740-531: A host with depressed resistance ( immunodeficiency ) or if they have unusual access to the inside of the body (for example, via trauma ). Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract , and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridioides difficile colitis ) or from
1885-502: A host. As bacterial and viral infections can both cause the same kinds of symptoms, it can be difficult to distinguish which is the cause of a specific infection. Distinguishing the two is important, since viral infections cannot be cured by antibiotics whereas bacterial infections can. There is a general chain of events that applies to infections, sometimes called the chain of infection or transmission chain . The chain of events involves several steps – which include
2030-521: A lesser extent, basic research in the biological sciences. Major areas of epidemiological study include disease causation, transmission , outbreak investigation, disease surveillance , environmental epidemiology , forensic epidemiology , occupational epidemiology , screening , biomonitoring , and comparisons of treatment effects such as in clinical trials . Epidemiologists rely on other scientific disciplines like biology to better understand disease processes, statistics to make efficient use of
2175-434: A link between virulence and transmissibility. Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as warts , cutaneous abscesses , respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about
2320-483: A number of genera , and are shown in this table. Each genus may be composed of many species , strains , or variants . Estimations of R 0 {\displaystyle R_{0}} for species, strains, and variants are typically less accurate than for genera, and so are provided in separate tables below for diseases of particular interest ( influenza and COVID-19 ). Estimates for strains of influenza . Estimates for variants of SARS-CoV-2 . In
2465-518: A number of basic dyes due to the electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as Giemsa stain or crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures
2610-463: A number of biological, sociobehavioral, and environmental factors. It can also be modified by physical distancing and other public policy or social interventions, although some historical definitions exclude any deliberate intervention in reducing disease transmission, including nonpharmacological interventions. And indeed, whether nonpharmacological interventions are included in R 0 {\displaystyle R_{0}} often depends on
2755-404: A particular pathogen at all (no matter how little) but also is often used in a sense implying a clinically apparent infection (in other words, a case of infectious disease). This fact occasionally creates some ambiguity or prompts some usage discussion; to get around this it is common for health professionals to speak of colonization (rather than infection ) when they mean that some of
2900-493: A pathogen from the appropriate clinical specimen. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Many pathogenic bacteria are easily grown on nutrient agar , a form of solid medium that supplies carbohydrates and proteins necessary for growth, along with copious amounts of water. A single bacterium will grow into
3045-429: A pathogen. A fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly. Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with
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#17327794809573190-432: A patient's blood or other body fluids for antigens or antibodies that indicate presence of a specific pathogen that the doctor suspects. Other techniques (such as X-rays , CAT scans , PET scans or NMR ) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by
3335-470: A persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise. Persistent infections cause millions of deaths globally each year. Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries. For infecting organisms to survive and repeat
3480-787: A population (endemic). The term "epidemiology" appears to have first been used to describe the study of epidemics in 1802 by the Spanish physician Joaquín de Villalba [ es ] in Epidemiología Española . Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic . The term epidemiology is now widely applied to cover the description and causation of not only epidemic, infectious disease, but of disease in general, including related conditions. Some examples of topics examined through epidemiology include as high blood pressure, mental illness and obesity . Therefore, this epidemiology
3625-520: A population-based health management framework called Life at Risk that combines epidemiological quantitative analysis with demographics, health agency operational research and economics to perform: Applied epidemiology is the practice of using epidemiological methods to protect or improve the health of a population. Applied field epidemiology can include investigating communicable and non-communicable disease outbreaks, mortality and morbidity rates, and nutritional status, among other indicators of health, with
3770-422: A prospective study, and confounders are more easily controlled for. However, they are more costly, and there is a greater chance of losing subjects to follow-up based on the long time period over which the cohort is followed. Cohort studies also are limited by the same equation for number of cases as for cohort studies, but, if the base incidence rate in the study population is very low, the number of cases required
3915-402: A random sample from the original population at risk. This has as a consequence that the control group can contain people with the disease under study when the disease has a high attack rate in a population. A major drawback for case control studies is that, in order to be considered to be statistically significant, the minimum number of cases required at the 95% confidence interval is related to
4060-403: A result of an infectious disease with immunosuppressive activity (such as with measles , malaria or HIV disease ). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host. While a primary infection can practically be viewed as the root cause of an individual's current health problem, a secondary infection
4205-471: A result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts. Opportunistic pathogens can cause an infectious disease in
4350-411: A severe illness affecting the brain, remain undiagnosed, despite extensive testing using the standard of care ( microbiological culture ) and state-of-the-art clinical laboratory methods. Metagenomic sequencing-based diagnostic tests are currently being developed for clinical use and show promise as a sensitive, specific, and rapid way to diagnose infection using a single all-encompassing test. This test
4495-417: A specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of AZT for the treatment of AIDS , the course of the disease was closely followed by monitoring
Basic reproduction number - Misplaced Pages Continue
4640-457: A threshold, even if calculated with different methods: if R 0 < 1 {\displaystyle R_{0}<1} , the outbreak will die out, and if R 0 > 1 {\displaystyle R_{0}>1} , the outbreak will expand. In some cases, for some models, values of R 0 < 1 {\displaystyle R_{0}<1} can still lead to self-perpetuating outbreaks. This
4785-445: A unique disease process different from any other individual ("the unique disease principle"), considering uniqueness of the exposome (a totality of endogenous and exogenous / environmental exposures) and its unique influence on molecular pathologic process in each individual. Studies to examine the relationship between an exposure and molecular pathologic signature of disease (particularly cancer ) became increasingly common throughout
4930-432: A visible mound on the surface of the plate called a colony , which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain ), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit
5075-412: Is "the expected number of secondary cases produced, in a completely susceptible population, produced by a typical infected individual". The basic reproduction number can be computed as a ratio of known rates over time: if a contagious individual contacts β {\displaystyle \beta } other people per unit time, if all of those people are assumed to contract the disease, and if
5220-509: Is a sequela or complication of that root cause. For example, an infection due to a burn or penetrating trauma (the root cause) is a secondary infection. Primary pathogens often cause primary infection and often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections (because immunodeficiency or injury was the predisposing factor). Other types of infection consist of mixed, iatrogenic , nosocomial , and community-acquired infection. A mixed infection
5365-399: Is a core component, that is unified with management science to provide efficient and effective health care and health guidance to a population. This task requires the forward-looking ability of modern risk management approaches that transform health risk factors, incidence, prevalence and mortality statistics (derived from epidemiological analysis) into management metrics that not only guide how
5510-507: Is active but does not produce noticeable symptoms may be called inapparent, silent, subclinical , or occult . An infection that is inactive or dormant is called a latent infection . An example of a latent bacterial infection is latent tuberculosis . Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family. The word infection can denote any presence of
5655-620: Is an illness resulting from an infection. Infections can be caused by a wide range of pathogens , most prominently bacteria and viruses . Hosts can fight infections using their immune systems . Mammalian hosts react to infections with an innate response, often involving inflammation , followed by an adaptive response. Specific medications used to treat infections include antibiotics , antivirals , antifungals , antiprotozoals , and antihelminthics . Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). The branch of medicine that focuses on infections
5800-423: Is an infection that is caused by two or more pathogens. An example of this is appendicitis , which is caused by Bacteroides fragilis and Escherichia coli . The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. A nosocomial infection is also one that occurs in a health care setting. Nosocomial infections are those that are acquired during
5945-422: Is an initial site of infection from which organisms travel via the bloodstream to another area of the body. Among the many varieties of microorganisms , relatively few cause disease in otherwise healthy individuals. Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depend upon
Basic reproduction number - Misplaced Pages Continue
6090-428: Is based upon how the pattern of the disease causes change in the function of human beings. The Greek physician Hippocrates , taught by Democritus, was known as the father of medicine , sought a logic to sickness; he is the first person known to have examined the relationships between the occurrence of disease and environmental influences. Hippocrates believed sickness of the human body to be caused by an imbalance of
6235-479: Is beyond the domain of the science of epidemiology. Epidemiology has its limits at the point where an inference is made that the relationship between an agent and a disease is causal (general causation) and where the magnitude of excess risk attributed to the agent has been determined; that is, epidemiology addresses whether an agent can cause disease, not whether an agent did cause a specific plaintiff's disease. In United States law, epidemiology alone cannot prove that
6380-510: Is currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases ( tetanus and botulism ). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins . A significant proliferation of
6525-483: Is disputed or is unclear, for presentation in legal settings. Epidemiological practice and the results of epidemiological analysis make a significant contribution to emerging population-based health management frameworks. Population-based health management encompasses the ability to: Modern population-based health management is complex, requiring a multiple set of skills (medical, political, technological, mathematical, etc.) of which epidemiological practice and analysis
6670-537: Is famous for his investigations into the causes of the 19th-century cholera epidemics, and is also known as the father of (modern) Epidemiology. He began with noticing the significantly higher death rates in two areas supplied by Southwark Company. His identification of the Broad Street pump as the cause of the Soho epidemic is considered the classic example of epidemiology. Snow used chlorine in an attempt to clean
6815-499: Is in the term inference . Correlation, or at least association between two variables, is a necessary but not sufficient criterion for the inference that one variable causes the other. Epidemiologists use gathered data and a broad range of biomedical and psychosocial theories in an iterative way to generate or expand theory, to test hypotheses, and to make educated, informed assertions about which relationships are causal, and about exactly how they are causal. Epidemiologists emphasize that
6960-418: Is increasing recognition that a wide range of modern data sources, many not originating from healthcare or epidemiology, can be used for epidemiological study. Such digital epidemiology can include data from internet searching, mobile phone records and retail sales of drugs. Epidemiologists employ a range of study designs from the observational to experimental and generally categorized as descriptive (involving
7105-503: Is injured. All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon , and an example of the latter are the various species of staphylococcus that exist on human skin . Neither of these colonizations are considered infections. The difference between an infection and
7250-424: Is not a biological constant for a pathogen as it is also affected by other factors such as environmental conditions and the behaviour of the infected population. R 0 {\displaystyle R_{0}} values are usually estimated from mathematical models, and the estimated values are dependent on the model used and values of other parameters. Thus values given in the literature only make sense in
7395-467: Is not an enzyme and has no metabolic function. Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon
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#17327794809577540-504: Is particularly problematic if there are intermediate vectors between hosts (as is the case for zoonoses ), such as malaria . Therefore, comparisons between values from the "Values of R 0 {\displaystyle R_{0}} of well-known contagious diseases" table should be conducted with caution. Although R 0 {\displaystyle R_{0}} cannot be modified through vaccination or other changes in population susceptibility, it can vary based on
7685-404: Is reduced by 1 ⁄ 2 . Although epidemiology is sometimes viewed as a collection of statistical tools used to elucidate the associations of exposures to health outcomes, a deeper understanding of this science is that of discovering causal relationships. " Correlation does not imply causation " is a common theme for much of the epidemiological literature. For epidemiologists, the key
7830-425: Is referred to as infectious diseases . Infections are caused by infectious agents ( pathogens ) including: The signs and symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue , loss of appetite, weight loss, fevers , night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes , coughing , or
7975-404: Is referred to as colonization. Most humans are not easily infected. Those with compromised or weakened immune systems have an increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections . Entrance to the host at host–pathogen interface , generally occurs through the mucosa in orifices like
8120-501: Is similar to current PCR tests; however, an untargeted whole genome amplification is used rather than primers for a specific infectious agent. This amplification step is followed by next-generation sequencing or third-generation sequencing , alignment comparisons , and taxonomic classification using large databases of thousands of pathogen and commensal reference genomes . Simultaneously, antimicrobial resistance genes within pathogen and plasmid genomes are sequenced and aligned to
8265-439: Is that microbial colonization is very common even in environments that humans think of as being nearly sterile . Because it is normal to have bacterial colonization, it is difficult to know which chronic wounds can be classified as infected and how much risk of progression exists. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in
8410-521: Is the average number of new infections caused by a single infected individual at time t in the partially susceptible population. It can be found by multiplying R 0 {\displaystyle R_{0}} by the fraction S of the population that is susceptible. When the fraction of the population that is immune increases (i. e. the susceptible population S decreases) so much that R e {\displaystyle R_{e}} drops below, herd immunity has been achieved and
8555-411: Is the mean-degree (average degree) of the network and ⟨ k 2 ⟩ {\displaystyle {\langle k^{2}\rangle }} is the second moment of the transmission network degree distribution . In populations that are not homogeneous, the definition of R 0 {\displaystyle R_{0}} is more subtle. The definition must account for
8700-398: Is the number of cases generated in the current state of a population, which does not have to be the uninfected state. R 0 {\displaystyle R_{0}} is a dimensionless number (persons infected per person infecting) and not a time rate, which would have units of time, or units of time like doubling time . R 0 {\displaystyle R_{0}}
8845-521: Is typically determined using DNA from peripheral blood leukocytes. Since the 2000s, genome-wide association studies (GWAS) have been commonly performed to identify genetic risk factors for many diseases and health conditions. While most molecular epidemiology studies are still using conventional disease diagnosis and classification systems, it is increasingly recognized that disease progression represents inherently heterogeneous processes differing from person to person. Conceptually, each individual has
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#17327794809578990-588: Is used in the taxonomic classification of microbes as well. Two methods, the Gram stain and the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Bacillota and Actinomycetota , both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota genera Mycobacterium and Nocardia . Biochemical tests used in
9135-439: Is used to describe the intersection of Host , Agent , and Environment in analyzing an outbreak. Case-series may refer to the qualitative study of the experience of a single patient, or small group of patients with a similar diagnosis, or to a statistical factor with the potential to produce illness with periods when they are unexposed. The former type of study is purely descriptive and cannot be used to make inferences about
9280-504: The Australian Department of Health , add the absence of "any deliberate intervention in disease transmission". The basic reproduction number is not necessarily the same as the effective reproduction number R {\displaystyle R} (usually written R t {\displaystyle R_{t}} [ t for time], sometimes R e {\displaystyle R_{e}} ), which
9425-605: The Journal of the American Medical Association 's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection. The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11–20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64–0.88) does not rule out infection (summary LR 0.64–0.88). Disease can arise if
9570-468: The oral cavity , nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids. Wound colonization refers to non-replicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue
9715-447: The polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids to cause
9860-512: The survival function , rearranging the largest eigenvalue of the Jacobian matrix , the next-generation method , calculations from the intrinsic growth rate, existence of the endemic equilibrium, the number of susceptibles at the endemic equilibrium, the average age of infection and the final size equation. Few of these methods agree with one another, even when starting with the same system of differential equations . Even fewer actually calculate
10005-476: The " one cause – one effect " understanding is a simplistic mis-belief. Most outcomes, whether disease or death, are caused by a chain or web consisting of many component causes. Causes can be distinguished as necessary, sufficient or probabilistic conditions. If a necessary condition can be identified and controlled (e.g., antibodies to a disease agent, energy in an injury), the harmful outcome can be avoided (Robertson, 2015). One tool regularly used to conceptualize
10150-403: The "strep test", they can be inexpensive. Complex serological techniques have been developed into what are known as immunoassays . Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of
10295-459: The "who, what, where and when of health-related state occurrence". However, analytical observations deal more with the 'how' of a health-related event. Experimental epidemiology contains three case types: randomized controlled trials (often used for a new medicine or drug testing), field trials (conducted on those at a high risk of contracting a disease), and community trials (research on social originating diseases). The term 'epidemiologic triad'
10440-515: The 2000s. However, the use of molecular pathology in epidemiology posed unique challenges, including lack of research guidelines and standardized statistical methodologies, and paucity of interdisciplinary experts and training programs. Furthermore, the concept of disease heterogeneity appears to conflict with the long-standing premise in epidemiology that individuals with the same disease name have similar etiologies and disease processes. To resolve these issues and advance population health science in
10585-504: The 2010s. By 2012, it was recognized that many pathogens' evolution is rapid enough to be highly relevant to epidemiology, and that therefore much could be gained from an interdisciplinary approach to infectious disease integrating epidemiology and molecular evolution to "inform control strategies, or even patient treatment." Modern epidemiological studies can use advanced statistics and machine learning to create predictive models as well as to define treatment effects. There
10730-439: The 2011 film Contagion , a fictional medical disaster thriller, a blogger's calculations for R 0 {\displaystyle R_{0}} are presented to reflect the progression of a fatal viral infection from isolated cases to a pandemic. Epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in
10875-560: The OR, a RR greater than 1 shows association, where the conclusion can be read "those with the exposure were more likely to develop the disease." Prospective studies have many benefits over case control studies. The RR is a more powerful effect measure than the OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated in a case control study where subjects are selected based on disease status. Temporality can be established in
11020-435: The ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. However, a host's immune system can also cause damage to the host itself in an attempt to control the infection. Clinicians, therefore, classify infectious microorganisms or microbes according to the status of host defenses – either as primary pathogens or as opportunistic pathogens . Primary pathogens cause disease as
11165-407: The assessment of data covering time, place, and person), analytic (aiming to further examine known associations or hypothesized relationships), and experimental (a term often equated with clinical or community trials of treatments and other interventions). In observational studies, nature is allowed to "take its course", as epidemiologists observe from the sidelines. Conversely, in experimental studies,
11310-400: The average number of secondary infections. Since R 0 {\displaystyle R_{0}} is rarely observed in the field and is usually calculated via a mathematical model, this severely limits its usefulness. Despite the difficulties in estimating R 0 {\displaystyle R_{0}} mentioned in the previous section, estimates have been made for
11455-458: The basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase , and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin
11600-414: The case control study. However, the point estimate generated is the relative risk (RR), which is the probability of disease for a person in the exposed group, P e = A / ( A + B ) over the probability of disease for a person in the unexposed group, P u = C / ( C + D ), i.e. RR = P e / P u . As with
11745-463: The case of viral identification, a region of dead cells results from viral growth, and is called a "plaque". Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent. In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as Mycobacterium leprae and Treponema pallidum can be grown in animals, although serological and microscopic techniques make
11890-429: The causation of the disease. Case-control studies are usually faster and more cost-effective than cohort studies but are sensitive to bias (such as recall bias and selection bias ). The main challenge is to identify the appropriate control group; the distribution of exposure among the control group should be representative of the distribution in the population that gave rise to the cases. This can be achieved by drawing
12035-476: The causative agent, Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case, xenodiagnosis involves the use of the vector of the Chagas agent T. cruzi , an uninfected triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of T. cruzi within its gut. Another principal tool in
12180-436: The cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve
12325-427: The cause-and-effect hypothesis and none can be required sine qua non ." Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in any particular case: Epidemiology is concerned with the incidence of disease in populations and does not address the question of the cause of an individual's disease. This question, sometimes referred to as specific causation,
12470-431: The composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of HIV in specific communities permitted the advancement of hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing
12615-553: The contact or disease transmission between them. If such a network is a locally tree-like network, then the basic reproduction can be written in terms of the average excess degree of the transmission network such that: R 0 = ⟨ k 2 ⟩ ⟨ k ⟩ − 1 , {\displaystyle R_{0}={\frac {\langle k^{2}\rangle }{\langle k\rangle }}-1,} where ⟨ k ⟩ {\displaystyle {\langle k\rangle }}
12760-468: The context of that model. Therefore, the contagiousness of different infectious agents cannot be compared without recalculating R 0 {\displaystyle R_{0}} with invariant assumptions. R 0 {\displaystyle R_{0}} values for past outbreaks might not be valid for current outbreaks of the same disease. Generally speaking, R 0 {\displaystyle R_{0}} can be used as
12905-484: The culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Many infectious organisms are identified without culture and microscopy. This is especially true for viruses, which cannot grow in culture. For some suspected pathogens, doctors may conduct tests that examine
13050-445: The data and draw appropriate conclusions, social sciences to better understand proximate and distal causes, and engineering for exposure assessment . Epidemiology , literally meaning "the study of what is upon the people", is derived from Greek epi 'upon, among' demos 'people, district' and logos 'study, word, discourse', suggesting that it applies only to human populations. However,
13195-400: The destruction of the virus. Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost-effective automated process for diagnosis of infectious disease. Technologies based upon
13340-428: The diagnosis of infectious disease is microscopy . Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound light microscope , or with instruments as complex as an electron microscope . Samples obtained from patients may be viewed directly under
13485-406: The disease cannot spread in the population because each infected person, on average, can only transmit the infection to less than one other contact. Conversely, the proportion of the population that remains susceptible to infection in the endemic equilibrium is 1 / R 0 {\displaystyle 1/R_{0}} . However, this threshold is based on simple models that assume
13630-409: The disease has a mean infectious period of 1 γ {\displaystyle {\dfrac {1}{\gamma }}} , then the basic reproduction number is just R 0 = β γ {\displaystyle R_{0}={\dfrac {\beta }{\gamma }}} . Some diseases have multiple possible latency periods, in which case the reproduction number for
13775-436: The disease overall is the sum of the reproduction number for each transition time into the disease. In reality, varying proportions of the population are immune to any given disease at any given time. To account for this, the effective reproduction number R e {\displaystyle R_{e}} or R {\displaystyle R} is used. R t {\displaystyle R_{t}}
13920-497: The disease to the cases in the series. A prospective study would involve following the case series over time to evaluate the disease's natural history. The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-up time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare the incidence rate of a given outcome between exposed and unexposed periods. This technique has been extensively used in
14065-424: The duration of infectivity of affected people, the contagiousness of the microorganism , and the number of susceptible people in the population that the infected people contact. The roots of the basic reproduction concept can be traced through the work of Ronald Ross , Alfred Lotka and others, but its first modern application in epidemiology was by George Macdonald in 1952, who constructed population models of
14210-445: The environment as a result of traumatic introduction (as in surgical wound infections or compound fractures ). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as chronic granulomatous disease ), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy ), exposure to ionizing radiation , or as
14355-612: The epidemiologist is the one in control of all of the factors entering a certain case study. Epidemiological studies are aimed, where possible, at revealing unbiased relationships between exposures such as alcohol or smoking, biological agents , stress , or chemicals to mortality or morbidity . The identification of causal relationships between these exposures and outcomes is an important aspect of epidemiology. Modern epidemiologists use informatics and infodemiology as tools. Observational studies have two components, descriptive and analytical. Descriptive observations pertain to
14500-771: The era of molecular precision medicine , "molecular pathology" and "epidemiology" was integrated to create a new interdisciplinary field of " molecular pathological epidemiology " (MPE), defined as "epidemiology of molecular pathology and heterogeneity of disease". In MPE, investigators analyze the relationships between (A) environmental, dietary, lifestyle and genetic factors; (B) alterations in cellular or extracellular molecules; and (C) evolution and progression of disease. A better understanding of heterogeneity of disease pathogenesis will further contribute to elucidate etiologies of disease. The MPE approach can be applied to not only neoplastic diseases but also non-neoplastic diseases. The concept and paradigm of MPE have become widespread in
14645-426: The expression of symptoms is often atypical, making a clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A rapid, sensitive, specific, and untargeted test for all known human pathogens that detects the presence of the organism's DNA rather than antibodies is therefore highly desirable. There is usually an indication for
14790-406: The fact that a typical infected individual may not be an average individual. As an extreme example, consider a population in which a small portion of the individuals mix fully with one another while the remaining individuals are all isolated. A disease may be able to spread in the fully mixed portion even though a randomly selected individual would lead to fewer than one secondary case. This is because
14935-571: The field and advanced methods to study cancer, a disease with patterns and mode of occurrences that could not be suitably studied with the methods developed for epidemics of infectious diseases. Geography pathology eventually combined with infectious disease epidemiology to make the field that is epidemiology today. Another breakthrough was the 1954 publication of the results of a British Doctors Study , led by Richard Doll and Austin Bradford Hill , which lent very strong statistical support to
15080-405: The four humors (black bile, yellow bile, blood, and phlegm). The cure to the sickness was to remove or add the humor in question to balance the body. This belief led to the application of bloodletting and dieting in medicine. He coined the terms endemic (for diseases usually found in some places but not in others) and epidemic (for diseases that are seen at some times but not others). In
15225-458: The general population of patients with that disease. These types of studies, in which an astute clinician identifies an unusual feature of a disease or a patient's history, may lead to a formulation of a new hypothesis. Using the data from the series, analytic studies could be done to investigate possible causal factors. These can include case-control studies or prospective studies. A case-control study would involve matching comparable controls without
15370-445: The given context and it is not recommended to compare values based on different models. R 0 {\displaystyle R_{0}} does not by itself give an estimate of how fast an infection spreads in the population. The most important uses of R 0 {\displaystyle R_{0}} are determining if an emerging infectious disease can spread in a population and determining what proportion of
15515-403: The growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of viruses : the medium, in this case, being cells grown in culture that the virus can infect, and then alter or kill. In
15660-447: The harder it is to control the epidemic. For simple models, the proportion of the population that needs to be effectively immunized (meaning not susceptible to infection) to prevent sustained spread of the infection has to be larger than 1 − 1 / R 0 {\displaystyle 1-1/R_{0}} . This is the so-called Herd immunity threshold or herd immunity level . Here, herd immunity means that
15805-484: The host's protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis . Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected with polio develop disease. On
15950-598: The host, preventing infection and speeding wound healing . The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include: As an example, several staphylococcal species remain harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum , multiply without resistance and cause harm. An interesting fact that gas chromatography–mass spectrometry , 16S ribosomal RNA analysis, omics , and other advanced technologies have made more apparent to humans in recent decades
16095-532: The identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species , the detection of fermentation products is commonly used in bacterial identification. Acids , alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media. The isolation of enzymes from infected tissue can also provide
16240-413: The infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Infection transmission can take place via many potential routes: The relationship between virulence versus transmissibility is complex; with studies have shown that there were no clear relationship between the two. There is still a small number of evidence that partially suggests
16385-399: The infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria. Given the wide range of bacterial, viral, fungal, protozoal, and helminthic pathogens that cause debilitating and life-threatening illnesses, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis ,
16530-402: The infectious agent, reservoir, entering a susceptible host, exit and transmission to new hosts. Each of the links must be present in a chronological order for an infection to develop. Understanding these steps helps health care workers target the infection and prevent it from occurring in the first place. Infection begins when an organism successfully enters the body, grows and multiplies. This
16675-425: The light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with biochemical staining techniques, and can be made exquisitely specific when used in combination with antibody based techniques. For example, the use of antibodies made artificially fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific antigens present on
16820-575: The link between tobacco smoking and lung cancer . In the late 20th century, with the advancement of biomedical sciences, a number of molecular markers in blood, other biospecimens and environment were identified as predictors of development or risk of a certain disease. Epidemiology research to examine the relationship between these biomarkers analyzed at the molecular level and disease was broadly named " molecular epidemiology ". Specifically, " genetic epidemiology " has been used for epidemiology of germline genetic variation and disease. Genetic variation
16965-403: The main etiological work that brought forward the concept. His concepts were still being considered in analysing SARS outbreak by WHO in 2004 in the context of traditional Chinese medicine. Another pioneer, Thomas Sydenham (1624–1689), was the first to distinguish the fevers of Londoners in the later 1600s. His theories on cures of fevers met with much resistance from traditional physicians at
17110-448: The middle of the 16th century, a doctor from Verona named Girolamo Fracastoro was the first to propose a theory that the very small, unseeable, particles that cause disease were alive. They were considered to be able to spread by air, multiply by themselves and to be destroyable by fire. In this way he refuted Galen 's miasma theory (poison gas in sick people). In 1543 he wrote a book De contagione et contagiosis morbis , in which he
17255-506: The multicausality associated with disease is the causal pie model . In 1965, Austin Bradford Hill proposed a series of considerations to help assess evidence of causation, which have come to be commonly known as the " Bradford Hill criteria ". In contrast to the explicit intentions of their author, Hill's considerations are now sometimes taught as a checklist to be implemented for assessing causality. Hill himself said "None of my nine viewpoints can bring indisputable evidence for or against
17400-502: The number of cases occurring in the population will gradually decrease to zero. Use of R 0 {\displaystyle R_{0}} in the popular press has led to misunderstandings and distortions of its meaning. R 0 {\displaystyle R_{0}} can be calculated from many different mathematical models . Each of these can give a different estimate of R 0 {\displaystyle R_{0}} , which needs to be interpreted in
17545-531: The number of new infections. The specific serological diagnostic identification, and later genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the temporal and geographical origins of the virus, as well as a myriad of other hypothesis. The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs . Molecular diagnostics are now commonly used to identify HIV in healthy people long before
17690-417: The odds of exposure in the cases (A/C) to the odds of exposure in the controls (B/D), i.e. OR = (AD/BC). If the OR is significantly greater than 1, then the conclusion is "those with the disease are more likely to have been exposed", whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is far less than one, then this suggests that the exposure is a protective factor in
17835-498: The odds ratio by the equation: where N is the ratio of cases to controls. As the odds ratio approaches 1, the number of cases required for statistical significance grows towards infinity; rendering case-control studies all but useless for low odds ratios. For instance, for an odds ratio of 1.5 and cases = controls, the table shown above would look like this: For an odds ratio of 1.1: Cohort studies select subjects based on their exposure status. The study subjects should be at risk of
17980-455: The onset of illness and have been used to demonstrate the existence of people who are genetically resistant to HIV infection. Thus, while there still is no cure for AIDS, there is great therapeutic and predictive benefit to identifying the virus and monitoring the virus levels within the blood of infected individuals, both for the patient and for the community at large. Symptomatic infections are apparent and clinical , whereas an infection that
18125-514: The other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease invariably kills all animals and people that are infected. Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain
18270-414: The outcome under investigation at the beginning of the cohort study; this usually means that they should be disease free when the cohort study starts. The cohort is followed through time to assess their later outcome status. An example of a cohort study would be the investigation of a cohort of smokers and non-smokers over time to estimate the incidence of lung cancer. The same 2×2 table is constructed as with
18415-929: The paper, disease, and what if any intervention is being studied. This creates some confusion, because R 0 {\displaystyle R_{0}} is not a constant; whereas most mathematical parameters with "nought" subscripts are constants. R {\displaystyle R} depends on many factors, many of which need to be estimated. Each of these factors adds to uncertainty in estimates of R {\displaystyle R} . Many of these factors are not important for informing public policy. Therefore, public policy may be better served by metrics similar to R {\displaystyle R} , but which are more straightforward to estimate, such as doubling time or half-life ( t 1 / 2 {\displaystyle t_{1/2}} ). Methods used to calculate R 0 {\displaystyle R_{0}} include
18560-539: The pathogens are present but that no clinically apparent infection (no disease) is present. Different terms are used to describe how and where infections present over time. In an acute infection, symptoms develop rapidly; its course can either be rapid or protracted. In chronic infection, symptoms usually develop gradually over weeks or months and are slow to resolve. In subacute infections, symptoms take longer to develop than in acute infections but arise more quickly than those of chronic infections. A focal infection
18705-456: The population should be immunized through vaccination to eradicate a disease. In commonly used infection models , when R 0 > 1 {\displaystyle R_{0}>1} the infection will be able to start spreading in a population, but not if R 0 < 1 {\displaystyle R_{0}<1} . Generally, the larger the value of R 0 {\displaystyle R_{0}} ,
18850-400: The prevailing Miasma Theory of the time, a model of disease in which poor air quality was blamed for illness. This was used to rationalize high rates of infection in impoverished areas instead of addressing the underlying issues of poor nutrition and sanitation, and was proven false by his work. Other pioneers include Danish physician Peter Anton Schleisner , who in 1849 related his work on
18995-640: The prevention of the epidemic of neonatal tetanus on the Vestmanna Islands in Iceland . Another important pioneer was Hungarian physician Ignaz Semmelweis , who in 1847 brought down infant mortality at a Vienna hospital by instituting a disinfection procedure. His findings were published in 1850, but his work was ill-received by his colleagues, who discontinued the procedure. Disinfection did not become widely practiced until British surgeon Joseph Lister 'discovered' antiseptics in 1865 in light of
19140-414: The purpose of communicating the results to those who can implement appropriate policies or disease control measures. Infectious disease An infection is the invasion of tissues by pathogens , their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease , also known as a transmissible disease or communicable disease ,
19285-402: The same population that gave rise to the cases. The case-control study looks back through time at potential exposures that both groups (cases and controls) may have encountered. A 2×2 table is constructed, displaying exposed cases (A), exposed controls (B), unexposed cases (C) and unexposed controls (D). The statistic generated to measure association is the odds ratio (OR), which is the ratio of
19430-747: The spread of malaria . In his work he called the quantity basic reproduction rate and denoted it by Z 0 {\displaystyle Z_{0}} . Compartmental models are a general modeling technique often applied to the mathematical modeling of infectious diseases . In these models, population members are assigned to 'compartments' with labels – for example, S, I, or R, (Susceptible, Infectious, or Recovered). These models can be used to estimate R 0 {\displaystyle R_{0}} . Epidemics can be modeled as diseases spreading over networks of contact and disease transmission between people. Nodes in these networks represent individuals and links (edges) between nodes represent
19575-456: The study of adverse reactions to vaccination and has been shown in some circumstances to provide statistical power comparable to that available in cohort studies. Case-control studies select subjects based on their disease status. It is a retrospective study. A group of individuals that are disease positive (the "case" group) is compared with a group of disease negative individuals (the "control" group). The control group should ideally come from
19720-457: The target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow
19865-559: The taxonomically classified pathogen genomes to generate an antimicrobial resistance profile – analogous to antibiotic sensitivity testing – to facilitate antimicrobial stewardship and allow for the optimization of treatment using the most effective drugs for a patient's infection. Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised . An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally,
20010-439: The term is widely used in studies of zoological populations (veterinary epidemiology), although the term " epizoology " is available, and it has also been applied to studies of plant populations (botanical or plant disease epidemiology ). The distinction between "epidemic" and "endemic" was first drawn by Hippocrates , to distinguish between diseases that are "visited upon" a population (epidemic) from those that "reside within"
20155-503: The test. For example, " Strep throat " is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, S. pyogenes , that is retrieved from a patient's throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration . Some serological methods are extremely costly, although when commonly used, such as with
20300-716: The time. He was not able to find the initial cause of the smallpox fever he researched and treated. John Graunt , a haberdasher and amateur statistician, published Natural and Political Observations ... upon the Bills of Mortality in 1662. In it, he analysed the mortality rolls in London before the Great Plague , presented one of the first life tables , and reported time trends for many diseases, new and old. He provided statistical evidence for many theories on disease, and also refuted some widespread ideas on them. John Snow
20445-523: The typical infected individual is in the fully mixed portion and thus is able to successfully cause infections. In general, if the individuals infected early in an epidemic are on average either more likely or less likely to transmit the infection than individuals infected late in the epidemic, then the computation of R 0 {\displaystyle R_{0}} must account for this difference. An appropriate definition for R 0 {\displaystyle R_{0}} in this case
20590-411: The use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent. Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of
20735-413: The water and removed the handle; this ended the outbreak. This has been perceived as a major event in the history of public health and regarded as the founding event of the science of epidemiology, having helped shape public health policies around the world. However, Snow's research and preventive measures to avoid further outbreaks were not fully accepted or put into practice until after his death due to
20880-637: The work of Louis Pasteur . In the early 20th century, mathematical methods were introduced into epidemiology by Ronald Ross , Janet Lane-Claypon , Anderson Gray McKendrick , and others. In a parallel development during the 1920s, German-Swiss pathologist Max Askanazy and others founded the International Society for Geographical Pathology to systematically investigate the geographical pathology of cancer and other non-infectious diseases across populations in different regions. After World War II, Richard Doll and other non-pathologists joined
21025-668: Was the first to promote personal and environmental hygiene to prevent disease. The development of a sufficiently powerful microscope by Antonie van Leeuwenhoek in 1675 provided visual evidence of living particles consistent with a germ theory of disease . During the Ming dynasty , Wu Youke (1582–1652) developed the idea that some diseases were caused by transmissible agents, which he called Li Qi (戾气 or pestilential factors) when he observed various epidemics rage around him between 1641 and 1644. His book Wen Yi Lun (瘟疫论, Treatise on Pestilence/Treatise of Epidemic Diseases) can be regarded as
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